P554: GILTERITINIB VERSUS SALVAGE CHEMOTHERAPY FOR RELAPSED/REFRACTORY FLT3-MUTATED ACUTE MYELOID LEUKEMIA: A PHASE 3, RANDOMIZED, MULTICENTER, OPEN-LABEL TRIAL IN ASIA
Authors: J. Wang, B. Jiang, J. Li, L. Liu, X. Du, H. Jiang, J. Hu, M. Yuan, T. Sakatani, T. Kadokura, M. Takeuchi, S. Izuka, L. Girshova, J. Tan, S. Bondarenko, L. L. L. Wong, A. Khuhapinant, E. Martynova, N. Hasabou, R. Tiu
Journal: HemaSphere (2022)

Background: Due to poor prognosis, treatment options for patients (pts) with relapsed/refractory to therapy (R/R) FLT3-mutated (FLT3mut+) acute myeloid leukemia (AML) are needed globally. The phase 3 ADMIRAL trial showed superior survival benefit and favorable safety for pts with R/R FLT3mut+ AML receiving gilteritinib vs salvage chemotherapy (SC); randomized, controlled trials of treatments in a mostly Asian population are lacking. Aims: We evaluated the efficacy and safety/tolerability of gilteritinib vs SC in Asian pts with R/R FLT3mut+ AML after first-line therapy. Methods: In this phase 3, open-label COMMODORE (NCT03182244) trial, adult pts in China, Russia, Singapore, Thailand, and Malaysia with R/R FLT3mut+ AML were randomized 1:1 to gilteritinib 120 mg orally per day or SC (low-dose cytarabine; mitoxantrone/etoposide/intermediate-dose cytarabine; or fludarabine/high-dose cytarabine/granulocyte colony-stimulating factor) over continuous 28-day cycles. Pts had ECOG score ≤2; pts with acute promyelocytic leukemia, BCR-ABL–positive leukemia, active central nervous system disease, or secondary AML were excluded. Primary endpoint was overall survival (OS); key secondary efficacy endpoints were event-free survival (EFS) and complete remission (CR). Other endpoints were duration of remission, composite CR (CRc), and safety/tolerability. OS and EFS were analyzed with stratified Cox proportional hazard models; response rates were analyzed with the Cochran-Mantel-Haenszel test. Subgroup analyses were planned. Interim analysis results are presented. Results: As of June 30, 2020, 234 pts were randomized (gilteritinib, n=116; SC, n=118). Median age was 51.5 and 49.5 years in the gilteritinib and SC groups, respectively; most pts had not received prior FLT3 inhibitors (87.9% and 93.2%). Baseline FLT3 mutations in the gilteritinib vs SC groups were: FLT3-ITD (91.4% vs 83.1%), FLT3-TKD (6.0% vs 11.9%), and both FLT3-ITD and FLT3-TKD (2.6% vs 5.1%). Median OS follow-up duration was 11.1 mo for gilteritinib and 6.9 mo for SC. Median OS was longer with gilteritinib (9.0 mo) vs SC (4.7 mo; HR 0.549 [95% CI: 0.379, 0.795]; P=0.00126); 1-year survival rate was 33.3% and 23.2%, respectively. OS benefit was seen with gilteritinib vs SC across most subgroups (Figure). Pts on gilteritinib had longer EFS than pts on SC (median EFS 2.8 vs 0.6 mo; HR 0.551 [95% CI: 0.395, 0.769]; P=0.00004). More pts had CR on gilteritinib (16.4%) vs SC (10.2%; P=0.17690); CRc rates were 50.0% and 20.3% (P<0.00001). Grade ≥3 adverse events (AEs) with gilteritinib (97.3%) vs SC (94.2%) were comparable; serious AE rates were higher for gilteritinib (73.5%) vs SC (61.5%). Adjusted for treatment exposure, AE rates were lower with gilteritinib (grade ≥3, 55.56 events/pt-year [E/PY]; serious, 6.19 E/PY) than SC (grade ≥3, 164.00 E/PY; serious, 12.40 E/PY). Most common AEs for gilteritinib were anemia (76.1%), thrombocytopenia (46.9%), pyrexia (41.6%), and increased blood lactate dehydrogenase (41.6%); for SC, most common AEs were anemia (64.4%), decreased white blood cell count (41.3%), and thrombocytopenia (38.5%). AEs leading to death occurred in 22 (19.5%) and 15 (14.4%) pts receiving gilteritinib or SC, respectively. Image:Summary/Conclusion: Gilteritinib significantly prolonged OS and EFS vs SC in pts with R/R FLT3mut+ AML in Asia. Safety/tolerability adjusted for treatment exposure was favorable for gilteritinib vs SC. COMMODORE results further validate/affirm the clinical efficacy/safety data from ADMIRAL, reinforcing the significant benefit of gilteritinib in R/R FLT3mut+ AML.